Deciphering the genotype and phenotype of hairy cell leukemia: clues for diagnosis and treatment

ABSTRACT

Introduction: Hairy cell leukemia (HCL) is a rare, indolent B-cell neoplasm. The classical variant of the disease is characterized by the BRAF V600E mutation, which is present in virtually all cases. How this mutation leads to the signs and symptoms of the disease is currently not known.

Areas covered: This review explores the genetic background of HCL, especially the BRAF V600E driver mutation, but passenger mutations and their effects are also included. The clinical significance of BRAF mutations in other cancer types is discussed, as well as BRAF- induced senescence. An overview of the major forms of treatment of HCL (cytostatic drugs, specific BRAF inhibitors, B cell-specific antibodies) is given. Finally, possible mechanisms of the monocytopenia and hairy morphology so typical of this disease are discussed.

Expert opinion: Although being a rare disease, HCL and its pathogenesis can yield important information about BRAF-related cancer metabolism. Many aspects of the disease are still unclear, but with the right resources, this could change. This can lead to a more efficient and specific treatment, thus leading to decreased morbidity.

KEYWORDS:

• BRAF mutations
• BRAF-induced senescence
• BRAF V600E mutation
• epidemiology
• genomic instability
• hairy cell leukemia
• hairy morphology
• immunophenotype
• monocytopenia

Article highlights

• Mutations in BRAF occur in many types of cancer and have varying effects.

• BRAF-induced senescence possibly contributes to/causes the low proliferation rate seen in HCL.

• Many patients show other mutations and chromosomal aberrations, but the lack of consistency makes them unlikely to have a major contribution to disease development.

• It is likely that the BRAF V600E mutation is related to both the hairy morphology of the cells and monocytopenia in HCL, but the direct molecular and cellular mechanisms underlying these phenomena remain unknown as yet.

Acknowledgments

We thank Mr. H. Scherrenburg (BSc) from the clinical chemistry laboratory of the Admiral de Ruyter Hospital in Goes for the light microscopy images of hairy cell leukemia cells.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.